It is the long-range purpose of this project to study how various chemicals and physiological changes affect xenobiotic metabolism by the body. This laboratory has concentrated its effort on the lung as a target organ for exposure to environmental stress. Present studies include isolation of rabbit lung cell types for the purpose of studying localization of xenobiotic metabolism within the lung and toxication-mechanisms in individual cell populations. Enzyme systems being used for study of individual xenobiotic metabolic pathways in lung cell populations: coumarin hydroxylase, 7-ethoxycoumarin deethylase, benzo(a)pyrene hydroxylase, epoxide hydrolase, and glutathione transferase. Different lung cell fractions (mixed cell populations) appear to have different metabolic profiles indicating possible differences in cytochrome content in the cell types. Enzyme activity is now being studied and compared in cell fractions containing either 80% alveolar type II cells or 70% nonciliated bronchiolar epithelial cells (Clara cells). The development of microspectrofluorometric techniques for the measurement of xenobiotic metabolism has enabled measurements to be made on single isolated cells, rather than on pooled fractions of cells.